Halichondrin B, a potent anticancer agent, was first isolated from the marine sponge Halichondria okadai. It is also found in Axinella sp., Phakellia carteri, and Lissondendryx sp. Halichondrin B has demonstrated in vitro inhibition of tubulin polymerization, microtubule assembly, betaS-tubulin crosslinking, GTP and vinblastine binding to tubulin, and tubulin-dependent GTP hydrolysis. It has also shown in vitro and in vivo anticancer activity.
Aicher, et al. published a total synthesis of halichondrin B in 1992. See Aicher, T. D. et al., J. Am. Chem. Soc. 114:3162-3164, and Zheng, W. J. et al., J. Bioorg. Med. Chem. Lett. 2004, 14, 5551. The syntheses of halichondrin B and various analogs have also been described in U.S. Pat. Nos. 6,214,865; 6,365,759; 6,469,182; and 6,653,341; in U.S. published patent applications 2004/0198806 and 2006/0104984; and in PCT published application WO 2005/118565, all of which are herein incorporated by reference in their entirety.